An example of the utility of genomic analysis for fast and accurate clinical diagnosis of complex rare phenotypes.

ABSTRACT:

Background

We describe molecular diagnosis in a complex consanguineous family: four offspring presented with combinations of three distinctive phenotypes; non-syndromic hearing loss (NSHL), an unusual skeletal phenotype comprising multiple fractures, cranial abnormalities and diaphyseal expansion, and significant developmental delay with microcephaly. We performed Chromosomal Microarray Analysis on the offspring with either the skeletal or developmental delay phenotypes, and linkage analysis and whole exome sequencing (WES) on all four children, parents and maternal aunt.

Results

Chromosomal microarray and FISH analysis identified a de novo unbalanced translocation as a cause of the microcephaly and severe developmental delay. WES identified a NSHL-causing splice variant in

SUBMITTER: Le Quesne Stabej P 

PROVIDER: S-EPMC5297239 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature